Vitamin D

The enzyme _________ catalyzes the conversion of 25-OH D to 1,25-(OH)D3

1α -hydroxylase

UVB radiation-> Vitamin D precursor in your skin-> _______ -> ________ -> active vitamin D

25- OH D 1.25- OH D

Metabolized to ______ in liver

25-OH D

______ secreted into blood, transported by DBP

25-OH D

With usual physiological intake, most vitamin D is converted to ______ and released into the blood; with supraphysiological intake, it is stored in the ______ tissue and released slowly.

25-OH D adipose

Ergocalciferol & cholecalciferol have a ______ with one ring broken Known as ______

3 ring structure Secosterioids

Structure of both Ergosterol & 7- dehydrocholesterol :

4-ring structure, characteristic of steroid

________ decreases the amount of calcium and phosphate in the blood.

Calcitonin

______ enables phosphorous absorption in the intestine

Calcitriol

_______ is loosely bound to DBPs for transport and then easy release into the tissues.

Calcitrol

Vitamin D reaching the liver either by way of ______ or by _____ must be hydroxylated by ________ to begin the generation of vitamin D's active form

Chylomicron remenants DBP cytochrome P-450 hydroxylases

_______ 25-OH D reflects Vit D status

Circulating

Most supplements provide Vit D as ______. Why?

D3 D3 is more potent than D2 form

______ known as vitamin D2 or calciferol, found in food and as dietary supplement

Ergocalciferol

Does dietary vitamin D require digestion?

No its absorbed from micelle by passive diffusion with help from bile salts and fat

From the blood, 25-OH D is taken up by tissues mostly the kidney in response to increase _____ concentrations.

PTH

A ______ is a substance added to a solid catalyst to improve its performance in a chemical reaction. By itself, the promoter has little or no catalytic effect. Some promoters interact with active components of catalysts and thereby alter their ______.

Promoter chemical effect on the catalyzed substance.

2 main function of Vit D

Serum Calcium Homeostasis Calcitrol synthesis Phosphorous homeostasis

Cutaneous vitamin D production is affected by time, pollution, latitude, sunscreen use, age, cloud cover, skin pigmentation. T of F

True

Sources of Vit D?

UV light, Animal foods fortified milk/dairy/margarine

First, Vit D activity requires an interaction with a ________.

Vitamin D Receptor (VDR)

Vitamin D exerts most of its effects via binding to a ______ that interacts with DNA. The vitamin D receptor is a member of the superfamily of _________ that regulate gene expression.

Vitamin D receptor (VDR) Nuclear receptors

Vit D deficiency

Widespread worldwide Rickets & Osteomalacia

Who needs supplementation?

breast-fed infants & other impaired absorption

The 1,25-(OH)D3 will be released to the blood and target the small intestinal cells to stimulate the production of ______, which is a calcium uptake protein. Collectively, all of these reactions will raise blood calcium levels to a normal physiological range.

calbindin

D3 is

cholecalciferol

Once within the enterocyte, vit D is incorporated into ______ that reach the systemic circulation via the _____ circulation. Some of the vit D is actually transferred from plasma chylomicrons to circulating ______

chylomicrons lymph vitamin D-binding proteins (DBP).

1α -hydroxylase is part of the enzyme systems associated with _________

cytochrome p450

D2 is

ergocalciferol

D3: Double bonds present at the ____ and _____ carbons in the B ring structure are necessary for this conversion, which in essence, opens up the B ring

fifth & seventh

Vit D carried aboard chylomicrons will be taken into _______ as chylomicrons remnants are removed. Meanwhile, the vitamin D transported by _____ can be delivered to extrahepatic tissue, such as skeletal muscle and adipocytes.

hepatocytes DBP

Both the liver and the kidneys add a ________ group to the vitamin D structure.

hydroxyl

Most absorbed in _______

jejunum

Vitamin D becomes incorporated into micelles in the small intestine and enters mucosal enterocytes by ________

passive diffusion

Low blood calcium increases secretion of _____. PTH stimulates (1) calcium release from bone; (2) 1 α-hydroxylase to produce 1,25 (OH)2D3 and (3) the reabsorption of calcium by the kidney tubules. 1,25 (OH)2 will enhance calcium absorption by stimulating small intestinal cells to produce the calcium uptake protein, calbindin. These series of reactions maintain calcium levels within a normal range.

PTH

Hypocalcemia (low blood calcium levels <8.5 mg/dL) will trigger _____

PTH release.

Role of ________ in the homeostatic control of calcium through interaction with vitamin D metabolism

Parathyroid hormone

Vit D toxicity Upper limit?

UL- 50 mg (4000 IU) most likely of all vitamins to cause toxicity excessive exposure to sun does not result in over production

The _______ may regulate the differentiation of hair follicles and skin epidermal cells.

VDR/1,25-dihydroxycholecalciferol

_______ are short sequences of DNA and are found in DNA regions associated with 1,25-dihydroxycholecalciferol-activated genes., such as ________, ________(expressed in osteoblasts), _______ (found in osteoclasts and macrophages) ______, and ______ (kidney).

VDREs Osteocalcin osteopontin β3 integrin 24-OHase calbindin D

Vitamin D binds to ____ & ___ complexes with ____ ____ influence gene expression/repression

VRD, VDR RXR VDRE's

In humans, ______ is created photochemically as UV light converts the precursor sterol 7-dehydrocholeserol to cholecalciferol. That reaction takes place as _______ glands secret 7-dehydrocholesterol onto the skins surface. Cholecalciferol can then be reabsorbed to varying depths within the skin.

Vitamin D3 Sebaceous

Osteomalacia

adults failure to mineralize already formed bone Results from decreased calcium and phosphate absorption

Why Vit D is still deemed essential

bc its recommended to avoid sun exposure to decrease risk of skin cancer

Vitamin D also called

calciferol

Parathyroid hormone stimulates ______ production in the kidney by increasing the synthesis of ______.

calcitrol 1-α hydroxylase.

PTH release will stimulate the release of ______ from bone.

calcium

The production of the vitamin D hormone is tightly feedback regulated directly or indirectly by _____ and ______ levels of the plasma

calcium & phosphorus

Whats major contributor of Vit D in human diet?

fortified milk and dairy products

Why is vitamin D questionable as a "vitamin"? What makes it unique...

*it can be synthesized* adequately in body with sufficient exposure to sunlight and organ function & it functions more like a *hormone* bc its activity is dependent on first interacting with a receptor

_______ min cutaneous exposure (Caucasian wearing a bathing suit) to UVB between 10 am -3 pm during spring, summer, fall produces ~10,000 - 20,000 IU (250-500 ug) of vitamin D3. About ______ times more than vitamin D found in fortified foods.

15-30 100

The most potent metabolite of vitamin D. This enzyme is found in renal cells lining the proximal tubule.

1a-hydroxylase

________ enables humans to manufacture vit D3 from UV light.

7-dehydrocholesterol

Provitamin is

7-dehydrocholesterol found in skin & breast milk

This vitamin D hormone functions in the intestine, bone, and kidney to stimulate transport of calcium and phosphorus into the extracellular fluid compartment upon demand.

Calcitriol (D3)

_______ maintains serum calcium levels by increasing calcium absorption in the gastrointestinal tract

Calcitrol

_______ acts on cells in the gastrointestinal tract to increase the production of calcium transport proteins, termed ________, which results in increased uptake of calcium from the gut into the body. This is the only mechanism by which the body can increase its calcium _____.

Calcitrol calbindin-D protein stores

______ is stimulated in response to changes in serum calcium concentrations and release of pTH

Calcitrol synthesis

PTH stimulates (1) _____ release from bone; (2) 1 α-hydroxylase to produce ________. (3) the reabsorption of calcium by the _______.

Calcium 1,25 (OH)2D3 Kidney tubules

Rickets Result?

Children Failure of bone to mineralize.As the epiphyseal cartilage continues to grow, it is not properly replaced with matrix and hydroxyapatite. Results in bowing of long, weight-bearing bones

_______ known as vitamin D3, made by the skin when exposed to light

Cholecalciferol

After hepatic synthesis, most 25-OH D is excreted from the liver and transported in the blood by _____. The blood is the major storage site of 25-OH D, which has a half-life of about 2-3 weeks

DBP

Upon reaching the liver, either by chylomicron remnant removal or by transport by ______, vitamin is hydroxylated at carbon 25 by ________. The status of existing active vitamin D is fundamental for the efficiency of this enzyme: when vit D status is low, efficiency increases. Vitamin D is converted to 25-hydrocholecalciferol, or more simply_______.

DBP 25 hydroxylase 25-OH D

Cytochrome P450 is involved in protein processing and transport (______) and the energy-producing centers of cells (_______)

ER mitochondria

______ converted to Vit D2 when irradiated with UV light

Ergosterol

These _______ are collectively referred to as mixed-function oxidases (the enzymes reduce one atom of molecular oxygen to water and one to the hydroxyl group) They are abbreviated by ____ followed by numbers/letters

Hydrolases CYP

Two medical conditions absorption can be compromised/decreased by ?

resection of jejunum fat malabsorption

The vitamin D receptor (VDR) acts in partnership with the_______ and binds to nucleotide base pairs called the _______ to control gene expression.

retinoic acid receptors (RXR) vitamin D-responsive elements (VDRE)

Direct exposure to UVB photons penetrate into the epidermis and dermis, allowing 7-dehydrocholesterol in the plasma membranes of skin cells to absorb the photons; this event causes the B ring to open, forming previtamin D3 (precholecalciferol). The unstable double bonds in previtamin D3 are rearranged through a process called ________.

thermal isomerization -atoms have diff arrangement

The efficiency of vitamin D binding is tremendously increased after ________ to its molecular form

two hydroxylations

Converted to 1,25-OH2 D (calcitriol) in kidneys Calcitrol released into _____

1,25-OH2 D blood

PTH will have two effects on the kidneys: 1) it will stimulate 1α -hydroxylase to produce ______ 2) it will stimulate the reabsorption of Ca by the _______

1,25-(OH)D3 kidney tubules

______ also picks up cholecalciferol created in the skin. About 40% circulating vit D is transported by ______, 60% by _____.

DBP chylomicrons DBP

Older adults produce less ______ and therefore produce up to ____ less Vit D.

DHCR7 75%

*Cis-retinoic acid* and *1,25-dihydroxycholecalciferol* are _____ that must be present to control gene expression.

Ligands

the activity of 1a- hydroxylase is enhanced by _____ & ______ and inhibited by ______ & ______

PTH & IGF-1 Calcium & phosphorous

Vitamin D _____ and ______ signaling pathways. ______ binds to its nuclear receptor (VDR) which, after heterodimerisation with ____, induces genomic responses.

genomic & nongenomic 1,25-(OH)2D RXR

In the kidneys, 25-OH D is _______at position 1 to form the vitamin's active form _______. Other tissues are also able to use _______ to make their own calcitriol.

hydroxylated *1,25-(OH)2* 25-OH D

Darker skin individuals require ______ sun exposure to generate the vitamin as melanin blocks some of the UVB rays.

longer

Incorporated into chylomicron for: -transport into ______, then _____ -transferred to ________ to skeletal muscle and adipocytes

lymphatic system, blood vitamin D binding proteins (DBP)

Vitamin D helps the small intestine and the kidney to reabsorb ______ back into the bloodstream. The _______ is believed to increase the brush border ______, which increases the availability of phosphorous for absorption by cleaving phosphate esters bonds with other molecules.

phosphate VDR/1,25-dihydroxycholecalciferol complex alkaline phosphatase

Calcitriol promotes reabsorption of ________ out of the bone and into the blood

phosphorous

Vitamin D Functions:

vitamin D receptor mediation regulation of gene expression differentiation of stem cells in bone tissue, hair follicles, and skin cells Possible roles in bone metabolism and/or bone formation and cancer -prevention and treatment Multiple sclerosis, type 1 diabetes, IBD and rheumatoid arthritis Thought to prevent heart disease of various types